Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Jun;84(3):449–453.

Elevated plasma interleukin-6 and increased severity and mortality in alcoholic hepatitis.

N Sheron 1, G Bird 1, J Goka 1, G Alexander 1, R Williams 1
PMCID: PMC1535433  PMID: 2044224

Abstract

Recent studies in alcoholic hepatitis have proposed a role for the cytokine tumour necrosis factor-alpha (TNF-alpha) a mediator of endotoxic shock in sepsis. In this study plasma levels of the closely related cytokine interleukin-6 (IL-6) were assayed in 96 samples from 58 patients with severe alcoholic hepatitis, and 69 patients in control groups (21 normal, 10 alcoholic without liver disease, 10 inactive alcoholic cirrhosis, 18 chronic liver disease, 10 chronic renal failure). Plasma IL-6 levels were markedly elevated in patients with alcoholic hepatitis when compared with all control groups (P less than 0.001). IL-6 levels were higher in patients who died (P = 0.04) and correlated with the features of severe disease including: increased grade of encephalopathy, increased neutrophil count, increased prothrombin ratio, hypotension, increased serum creatinine and increased serum bilirubin. Surprisingly, no correlation was found between levels of plasma IL-6 and plasma TNF-alpha or endotoxin, or the presence of infection; an inverse correlation was found between plasma IL-6 and serum globulins. These findings provide further evidence that the IL-6/TNF cytokine system is activated in severe alcoholic hepatitis and may mediate hepatic or extra-hepatic tissue damage.

Full text

PDF
449

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  2. Bird G. L., Sheron N., Goka A. K., Alexander G. J., Williams R. S. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med. 1990 Jun 15;112(12):917–920. doi: 10.7326/0003-4819-112-12-917. [DOI] [PubMed] [Google Scholar]
  3. Castell J. V., Geiger T., Gross V., Andus T., Walter E., Hirano T., Kishimoto T., Heinrich P. C. Plasma clearance, organ distribution and target cells of interleukin-6/hepatocyte-stimulating factor in the rat. Eur J Biochem. 1988 Nov 1;177(2):357–361. doi: 10.1111/j.1432-1033.1988.tb14384.x. [DOI] [PubMed] [Google Scholar]
  4. Cruickshank A. M., Fraser W. D., Burns H. J., Van Damme J., Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond) 1990 Aug;79(2):161–165. doi: 10.1042/cs0790161. [DOI] [PubMed] [Google Scholar]
  5. Deviere J., Content J., Denys C., Vandenbussche P., Schandene L., Wybran J., Dupont E. High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production. Clin Exp Immunol. 1989 Aug;77(2):221–225. [PMC free article] [PubMed] [Google Scholar]
  6. Fong Y. M., Marano M. A., Moldawer L. L., Wei H., Calvano S. E., Kenney J. S., Allison A. C., Cerami A., Shires G. T., Lowry S. F. The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans. J Clin Invest. 1990 Jun;85(6):1896–1904. doi: 10.1172/JCI114651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fong Y., Tracey K. J., Moldawer L. L., Hesse D. G., Manogue K. B., Kenney J. S., Lee A. T., Kuo G. C., Allison A. C., Lowry S. F. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989 Nov 1;170(5):1627–1633. doi: 10.1084/jem.170.5.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Helle M., Brakenhoff J. P., De Groot E. R., Aarden L. A. Interleukin 6 is involved in interleukin 1-induced activities. Eur J Immunol. 1988 Jun;18(6):957–959. doi: 10.1002/eji.1830180619. [DOI] [PubMed] [Google Scholar]
  9. Imperiale T. F., McCullough A. J. Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials. Ann Intern Med. 1990 Aug 15;113(4):299–307. doi: 10.7326/0003-4819-113-4-299. [DOI] [PubMed] [Google Scholar]
  10. Le J. M., Vilcek J. Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response. Lab Invest. 1989 Dec;61(6):588–602. [PubMed] [Google Scholar]
  11. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sehgal P. B., Helfgott D. C., Santhanam U., Tatter S. B., Clarick R. H., Ghrayeb J., May L. T. Regulation of the acute phase and immune responses in viral disease. Enhanced expression of the beta 2-interferon/hepatocyte-stimulating factor/interleukin 6 gene in virus-infected human fibroblasts. J Exp Med. 1988 Jun 1;167(6):1951–1956. doi: 10.1084/jem.167.6.1951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sheron N., Lau J. Y., Daniels H. M., Webster J., Eddleston A. L., Alexander G. J., Williams R. Tumour necrosis factor to treat chronic hepatitis B virus infection. Lancet. 1990 Aug 4;336(8710):321–322. doi: 10.1016/0140-6736(90)91866-9. [DOI] [PubMed] [Google Scholar]
  14. Theodossi A., Eddleston A. L., Williams R. Controlled trial of methylprednisolone therapy in severe acute alcoholic hepatitis. Gut. 1982 Jan;23(1):75–79. doi: 10.1136/gut.23.1.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Waage A., Brandtzaeg P., Halstensen A., Kierulf P., Espevik T. The complex pattern of cytokines in serum from patients with meningococcal septic shock. Association between interleukin 6, interleukin 1, and fatal outcome. J Exp Med. 1989 Jan 1;169(1):333–338. doi: 10.1084/jem.169.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Waage A., Halstensen A., Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. doi: 10.1016/s0140-6736(87)91728-4. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES